title: Antitumor effect of fructose 1,6-bisphosphate and its mechanism in hepatocellular carcinoma cells.
abstract: We aimed to investigate the antitumor effect and mechanism of fructose 1,6-bisphosphate (F1,6BP) in a hepatocellular carcinoma cell line. HepG2 cells were treated with different concentrations of F1,6BP alone or in combination with antioxidant N-acetyl-L-cysteine (NAC) or catalase (CAT), and cell proliferation assays were performed. Nuclear morphology was observed by fluorescence microscopy after Hoechst staining, and apoptosis was measured with flow cytometry. Changes in reactive oxygen species (ROS) levels in HepG2 cells were detected by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining. A colorimetric assay was adopted to determine the percentage of oxidized glutathione in these cells. CAT and glutathione peroxidase (GSH-Px) mRNA expression levels in HepG2 cells were measured by real-time fluorescence quantitative PCR. HepG2 cell proliferation was significantly inhibited by F1,6BP, accompanied by an increase in intracellular ROS levels and oxidized glutathione. Upregulated apoptosis and characteristic nuclear morphological changes were observed, and the expression of CAT and GSH-Px mRNA was increased after F1,6BP treatment. The antitumor effect of F1,6BP was significantly decreased after pretreatment with NAC and CAT in HepG2 cells. In conclusion, F1,6BP can induce the apoptosis of HepG2 cells. The mechanism involved may be associated with the generation of ROS, especially the production of H2O2.
authors.affiliation: Cancer Center, Xinchang People's Hospital, Zhejiang, China, YinXiang_Lu@126.com.
authors.forename: Yin-Xiang
authors.initials: YX
authors.lastname: Lu
authors.forename: Xi-Can
authors.initials: XC
authors.lastname: Yu
authors.forename: Mei-Ying
authors.initials: MY
authors.lastname: Zhu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D049109:Cell Proliferation; D005635:Fructosediphosphates / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; C029063:fructose-1,6-diphosphate; D000111:Acetylcysteine